Beyond Marfan: the clinical impact of bronchiectasis and non-tuberculous mycobacteria in connective tissue diseases

We read with great interest the study by Hwang et al., in a recent issue of the Journal, which highlighted the considerable radiographic burden of bronchiectasis in this population.¹ While no patients in the series were ultimately diagnosed with clinically significant pulmonary non-tuberculous mycobacteria (PNTM) infections, the body morphotype overlap between PNTM patients and connective tissue disease (CTD) patients has long been noted in the literature.² We have recently reported, for example, that 90% of PNTM-affected patients have variants in connective tissue-related genes.³

Whether the radiographic findings reported by Hwang et al. are clinically meaningful was left unanswered by the authors. Our experience, derived from a population of 103 CTD patients (24 with Marfan syndrome, 76 with Ehlers-Danlos syndrome and 3 with MASS [mitral valve, aorta, skeleton and skin] syndrome), suggests that pulmonary symptoms may be significant. Using both a retrospective chart review as well as telephone surveys of these patients, we found that 28 (42%) reported chronic cough, 6 (9%) chronic sputum production, 14 (21%) haemoptysis, 26 (39%) dyspnoea and 17 (26%) wheezing. As only 44 had undergone chest computed tomography (CT) imaging, we were only able to uncover 4 (9%) with bronchiectasis, which may be an underestimation of the true prevalence. Of the four patients with radiographic bronchiectasis, only one had the diagnosis of Marfan syndrome; two had Ehlers-Danlos syndrome and 1 had MASS syndrome.

Unlike the cohort studied by Hwang et al., we found two cases of clinically significant PNTM. Case #1 was a 58-year-old female with MASS syndrome who was found to have extensive bronchiectasis in the right middle lobe and lingula after developing haemoptysis. Sputum cultures ultimately grew Mycobacterium avium complex (MAC). Despite multiple treatment regimens, her MAC proved resistant to antibiotics and she ultimately died 12 years after initial presentation from declining respiratory status and emaciation. Case #2 was a 58-year-old female with Ehlers-Danlos syndrome who was incidentally found to have nodularity and scarring in the right lower lobe after a chest CT was performed for cancer staging purposes (the patient had a history of thyroid cancer). Open lung biopsy cultures grew MAC. She remains on treatment with azithromycin, ethambutol and rifampicin, and has since had interval development of bronchiectasis on CT imaging.

Our experience suggests first that the bronchiectasis discovered by Hwang et al. may not be an innocent radiographic finding. Providers of CTD patients should have a low threshold to assess patients for pulmonary symptoms and furthermore to image symptomatic patients with chest CT imaging. Investigation for PNTM is also warranted in this population. Those with symptomatic bronchiectasis may find benefit from airway clearance devices and nebulised hypertonic saline, and anti-mycobacterial therapy should be considered in those testing positive for PNTM. Second, our findings suggest that this phenomenon may not be limited to Marfan syndrome, but that other CTD entities such as Ehlers-Danlos syndrome may also be implicated. Greater awareness of bronchiectasis and PNTM amongst clinicians caring for CTD patients is needed, given what may be important clinical burdens in this population.